Validating critical analytical variables of a multiplexed gene expression assay measuring tumor inflammation designed to predict response to anti-PD1 therapy
| Autor: | Patrick Danaher, Brett Wallden, Simina Popa, Xing Ren, Carl Schaper, Sean Ferree, Sarah E. Church, Irena Pekker, Naeem Dowidar, Celine Ngouenet, Amy Sullivan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Formalin fixed paraffin embedded business.industry RNA Computational biology Biomarker (cell) 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Rna expression Oncology 030220 oncology & carcinogenesis Gene expression Medicine Single agent Anti pd1 Solid tumor business |
| Zdroj: | Journal of Clinical Oncology. 36:203-203 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2018.36.5_suppl.203 |
| Popis: | 203 Background: The development and analytical performance of the Tumor Inflammation Signature (TIS) assay has been described previously. The TIS is an investigational use RNA expression assay on the nCounter Dx Analysis System, which is being evaluated as a patient enrichment biomarker for treatment with pembrolizumab single agent across multiple solid tumor types. Here we describe the analytical validation of the RNA input range and analytical precision starting from RNA isolated from formalin fixed paraffin embedded (FFPE) tissue blocks. Methods: Analytical validation of TIS assay performance across an RNA input range was performed using samples from 11 tumor types. The analytical precision between sites, instruments, reagent lots, and users was measured, using RNA samples isolated from FFPE tissue blocks. Results: The assay was validated across the specified RNA input range with ≥ 94% concordance at the minimum specified RNA input (50ng). The total standard deviation of the TIS score was < 0.04 units across three sites with ≥98% concordance between sites. The 6 users across the three sites did not significantly contribute to the assay variability. There was 100% concordance in biomarker high/low categorization between multiple reagent lots and multiple instruments. Conclusions: The analytical performance of the NanoString TIS assay has been validated to give consistent results across the RNA input range and between site, instrument, assay user, and reagent kit lot. The assay is well suited for decentralized clinical testing and is currently under investigation as a biomarker to enrich for response to anti-PD1 therapy across multiple tumor types. |
| Databáze: | OpenAIRE |
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